P1.11. THE ROLE OF DOPAMINE-SENSITIVE MOTOR CORTICAL CIRCUITS IN THE DEVELOPMENT AND EXECUTION OF SKILLED FORELIMB MOVEMENTS
Martyna Gorkowska-Nosal1,2, Gniewosz Drwięga1, Łukasz Szumiec3, Jan Rodriguez Parkita3, Przemysław E. Cieślak1
1 Jagiellonian University, Institute of Zoology and Biomedical Research, Department of Neurophysiology and Chronobiology, 9 Gronostajowa St., Krakow, Poland
2 Jagiellonian University, Doctoral School of Exact and Natural Sciences, 11 Łojasiewicza St., Krakow, Poland
3 Maj Institute of Pharmacology Polish Academy of Sciences, Department of Molecular Neuropharmacology, 12 Smętna St., Krakow, Poland
INTRODUCTION: The primary motor cortex (M1) plays a key role in controlling voluntary movements and is innervated by dopaminergic fibers. There is growing evidence that dopamine (DA) transmission in M1 is crucial for motor skill learning.
AIM(S): Nevertheless, the spatiotemporal DA dynamics and activity patterns of DA-sensitive neuronal populations in the M1, during the formation and execution of skilled forelimb movements, have not yet been investigated.
METHOD(S): We have developed a forelimb-specific joystick task for head-fixed animals and used fiber photometry to track DA dynamics and population-level calcium (Ca2+) activity in the M1 of D1Cre and D2Cre mice, during the development of skilled behavior, and following subsequent changes in reward threshold and contingency. Furthermore, we determined the laminar distribution of D1 receptor-positive (D1+) and D2 receptor-positive (D2+) cells in the M1, employed retrograde tracings to determine their long-range connections, and used reversible optogenetic inhibition to investigate their functional contribution to motor performance.
RESULTS: We found that DA release events and Ca2+ transients were temporally associated with joystick movements and reward consumption. Moreover, DA dynamics and the population-level activity of DA-receptive neurons scaled with the vigor of forelimb movements and tracked the relationship between actions and their outcomes. We showed that D1+ and D2+ neurons have a discrete distribution in the layers of the M1, with D1+ neurons primarily found in the deep layers, and D2+ cells distributed in the superficial layers. We also showed that only a small fraction of D1+ and D2+ projection neurons of the M1 contact long-range targets. Finally, we found that when cortical inhibition was released, the number of rewarded joystick movements in D1Cre and D2Cre animals decreased.
CONCLUSIONS: Overall, our findings show how phasic DA signals in the M1 facilitate reinforcement motor learning of skilled behavior.
FINANCIAL SUPPORT: National Science Centre, Poland – SONATA 2020/39/D/NZ4/00503